TMC207 +/- Rifabutin/Rifampin

32 (16 per treatment group) healthy male or female subjects, 18 - 45 years old will be
enrolled.Subjects will receive two single oral doses of 400mg TMC207, first on Study Day 1
followed by a 28-day wash-out, the second on Study Day 29. On Study Day 28, any abnormal
safety labs will be reviewed by study physician and be determined not to meet the exclusion
criteria before administration of the second dose of TMC207. Rifabutin 300mg (Group 1) or
rifampin 600mg (Group 2) will be administered once daily during Period 2 from Study Day 20
through Study Day 41. The primary endpoint for the study (pharmacokinetics, safety and
tolerability of TMC207 (and its M2 metabolite) will be determined on the final study visit,
Day 57 (28 days after the last TMC207 dose in Period 2).

Inclusion Criteria:

-Aged between 18 and 45 years, extremes included. -Non tobacco/nicotine using (at least 3
months prior to screening). -Body Mass Index (BMI, weight in kg divided by the square of
height in meters) of 18.0 to <35.0 kg/m^2 -Informed Consent Form (ICF) signed voluntarily
before the first trial-related activity. -Able to comply with protocol requirements.
-Healthy on the basis of a medical evaluation or history that reveals the absence of any
clinically relevant abnormality and includes a physical examination, medical history,
electrocardiogram (ECG), vital signs, ophthalmologic exam, the results of blood
biochemistry, and hematology tests, and a urinalysis carried out at screening (See Section
7.2). -Subjects will be enrolled in this study only if they have undergone
vasectomy/complete hysterectomy, tubal ligation, or other sterilizing procedure, or the
subject is a post-menopausal woman for more than two years, or if sexually active subjects
agree to use two of the following forms of adequate contraception during the study and for
12 weeks after the final dose: abstinence, condoms with or without spermicide gel,
diaphragm with spermicide gel, hormonal or non-hormonal intrauterine device, oral
contraceptive pills, and depot progesterone injections. If a subject is usually not
sexually active but becomes active, the subject and his or her partner must use two of the
listed contraceptive methods.

Exclusion Criteria:

Medical History -History or evidence of current use of alcohol, barbiturate, amphetamine,
recreational, or narcotic drug use, which in the investigator's opinion would compromise
subject's safety and/or compliance with the trial procedures. -Any clinically significant
(as deemed by the Principal Investigator) history of acute illness (resolved within 4
weeks of screening), asthma, or presence of cardiovascular, pulmonary, hepatic, renal,
hematologic, gastrointestinal (including eating disorders), endocrine, metabolic,
immunologic, dermatologic, neurologic, psychological, or psychiatric disease. -Currently
significant diarrhea, gastric stasis, or constipation that in the investigator's opinion
could influence drug absorption or bioavailability. -Any history of significant skin
disease such as, but not limited to, rash or eruptions, drug allergies, food allergy,
dermatitis, eczema, psoriasis, or urticaria. Subjects with a history of skin disease may
be enrolled into the study after consultation with the Sponsor Medical Monitor.
-Previously demonstrated clinically significant allergy or hypersensitivity to any of the
excipients of the investigational medication administered in this trial (i.e., rifabutin,
rifampin, and TMC207). -Subjects with QTcB [Bazett correction] interval > 450ms at
screening -Subjects with any other clinically significant Electrocardiogram (ECG)
abnormality at screening, such as arrhythmia, ischemia, or evidence of heart failure or
with a family history of Long QT Syndrome. -History or evidence of ophthalmologic diseases
except for routine corrected hyperopia, myopia, and presbyopia. -Recent history (within
past 30 days) of vertigo/nausea. Specific Treatments -Current use of any azole antifungal
agent -Use of concomitant medication, including over-the-counter products and dietary
supplements, without approval from study staff. Subjects will be treated based on symptom
presentation, with the exception of medications that affect p450 and 3a metabolic pathways
(refer to the MOP for a list of acceptable medications). During outpatient time periods,
subjects will be required to discuss with the study staff and receive approval before
self-administering any medication. After gaining approval, subjects will also be asked to
record any medication taken during outpatient time periods in a provided log.
-Participation in an investigational drug trial within 60 days prior to the first intake
of trial medication and during the duration of the study. -Donation of blood or
significant loss of blood within 56 days or plasma donation within 7 days preceding the
first intake of trial medication. -Having received TMC207 in a previous trial. Based on
Laboratory Abnormalities -Positive HIV-1 or HIV-2 test by Enzyme-linked immunosorbent
assay (ELISA) at screening. -Hepatitis A, B, or C infection (confirmed by hepatitis A
antibody IgM, hepatitis B surface antigen, or hepatitis C virus antibody, respectively) at
screening. -A positive urine drug test at screening. Urine will be tested to check the
current use of amphetamines, benzodiazepines, cocaine, cannabinoids, and opioids; along
with serum alcohol level. -Subjects with the following laboratory abnormalities at
screening as defined by the National Institute of Health (NIH), National Institute of
Allergy and Infectious Diseases (NIAID), Division of Microbiology and Infectious Diseases
(DMID) Adult Toxicity Table (Appendix C) and in accordance with the normal ranges of the
clinical laboratory: a.Serum creatinine grade 1 or greater [> 1.0 x Upper limit of lab
normal range (ULN)], b.Pancreatic lipase grade 1 or greater (> 1.0 x ULN), c.Hemoglobin
grade 1 or greater ( e.Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) grade 1 or greater (>
1.0 x ULN), f.Total bilirubin grade 1 or greater (> 1.0 x ULN), g.Creatine kinase grade 1
or greater (>1.0 x ULN), h.Troponin grade 1 or greater (1.0 x UNL), or i.Any other
toxicity grade 2 or above, including: proteinuria (spot urine) > 1+ and gross hematuria.
For the second dose of TMC207, any other toxicity grade 3 or above, including: proteinuria
(spot urine) > 1+ and gross hematuria